STUDIES WITH TRANSFECTED AND PERMEABILIZED RBL-2H3 CELLS REVEAL UNIQUE INHIBITORY PROPERTIES OF PROTEIN-KINASE C-GAMMA

To characterize protein kinase C (PKC)gamma, an isozyme found exclusiv ely in brain and spinal cord, its cDNA was introduced into basophilic RBL-2H3 cells that lack this isozyme. The expression of PKC gamma sign ificantly attenuated antigen-induced responses including hydrolysis of inositol phospholipids, increase in cytosolic calcium, and secretion of granules but enhanced antigen-induced release of arachidonic acid. Instead of a sustained increase in cytosolic calcium, antigen now indu ced calcium oscillations; possibly as a consequence of suppression of phospholipase C activity and incomplete emptying of internal calcium s tores. In addition, PKC gamma appeared to inhibit activation of other PKC isozymes because phorbol 12-myristate 13-acetate failed to act syn ergistically with the Ca2+ ionophore on secretion. This was confirmed in other studies where PKC gamma was shown to suppress the transductio n of stimulatory signals by other isozymes of PKC on provision of thes e isozymes to PKC-depleted permeabilized cells. The studies in total i ndicated that only PKC gamma was capable of inhibiting both early and distal signals for secretion including those signals transduced by end ogenous isozymes of PKC.